{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:40:32Z","timestamp":1791355232717,"version":"4.3.1"},"reference-count":213,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T00:00:00Z","timestamp":1647388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"A.R.C.","award":["19\/23-21"],"award-info":[{"award-number":["19\/23-21"]}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["772418"],"award-info":[{"award-number":["772418"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002661","name":"Fund for Scientific Research","doi-asserted-by":"publisher","award":["\/"],"award-info":[{"award-number":["\/"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Walloon Excellence in Lifesciences and Biotechnology","award":["\/"],"award-info":[{"award-number":["\/"]}]},{"name":"Fondation contre le cancer (Belgium)","award":["\/"],"award-info":[{"award-number":["\/"]}]},{"name":"Fonds sp\u00e9ciaux de la recherche (University of Li\u00e8ge)","award":["\/"],"award-info":[{"award-number":["\/"]}]},{"name":"FHULF (University of Li\u00e8ge)","award":["\/"],"award-info":[{"award-number":["\/"]}]},{"name":"European Union's Horizon 2020 research and innovation programme","award":["874708"],"award-info":[{"award-number":["874708"]}]},{"name":"European Union's Horizon 2020 research and innovation programme","award":["FP\/2014-2020"],"award-info":[{"award-number":["FP\/2014-2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Lymphangiogenesis (LA) is the formation of new lymphatic vessels by lymphatic endothelial cells (LECs) sprouting from pre-existing lymphatic vessels. It is increasingly recognized as being involved in many diseases, such as in cancer and secondary lymphedema, which most often results from cancer treatments. For some cancers, excessive LA is associated with cancer progression and metastatic dissemination to the lymph nodes (LNs) through lymphatic vessels. The study of LA through in vitro, in vivo, and, more recently, in silico models is of paramount importance in providing novel insights and identifying the key molecular actors in the biological dysregulation of this process under pathological conditions. In this review, the different biological (in vitro and in vivo) models of LA, especially in a cancer context, are explained and discussed, highlighting their principal modeled features as well as their advantages and drawbacks. Imaging techniques of the lymphatics, complementary or even essential to in vivo models, are also clarified and allow the establishment of the link with computational approaches. In silico models are introduced, theoretically described, and illustrated with examples specific to the lymphatic system and the LA. Together, these models constitute a toolbox allowing the LA research to be brought to the next level.<\/jats:p>","DOI":"10.3390\/cancers14061525","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T22:09:58Z","timestamp":1647468598000},"page":"1525","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["In Vitro, In Vivo, and In Silico Models of Lymphangiogenesis in Solid Malignancies"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5892-8723","authenticated-orcid":false,"given":"Sophie","family":"Bekisz","sequence":"first","affiliation":[{"name":"Biomechanics Research Unit, GIGA In silico Medicine, ULi\u00e8ge, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Baudin","sequence":"additional","affiliation":[{"name":"Laboratory of Biology of Tumor and Development, GIGA Cancer, ULi\u00e8ge, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Buntinx","sequence":"additional","affiliation":[{"name":"Laboratory of Biology of Tumor and Development, GIGA Cancer, ULi\u00e8ge, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"No\u00ebl","sequence":"additional","affiliation":[{"name":"Laboratory of Biology of Tumor and Development, GIGA Cancer, ULi\u00e8ge, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8180-1445","authenticated-orcid":false,"given":"Liesbet","family":"Geris","sequence":"additional","affiliation":[{"name":"Biomechanics Research Unit, GIGA In silico Medicine, ULi\u00e8ge, 4000 Li\u00e8ge, Belgium"},{"name":"Biomechanics Section, KU Leuven, 3000 Leuven, Belgium"},{"name":"Skeletal Biology and Engineering Research Center, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,16]]},"reference":[{"key":"ref_1","unstructured":"(2021, August 23). World Health Organization. Available online: https:\/\/www.who.int\/health-topics\/cancer#tab=overview."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The Next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1080\/07357900701662509","article-title":"Tumoral Angiogenesis: Review of the Literature","volume":"26","author":"Shahi","year":"2008","journal-title":"Cancer Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"761671","DOI":"10.1155\/2010\/761671","article-title":"Tumor Angiogenesis","volume":"2010","author":"Dudek","year":"2010","journal-title":"J. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1007\/s00018-019-03351-7","article-title":"Tumor angiogenesis: Causes, consequences, challenges and opportunities","volume":"77","author":"Lugano","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s13402-016-0281-9","article-title":"The role of lymphangiogenesis and angiogenesis in tumor metastasis","volume":"39","author":"Paduch","year":"2016","journal-title":"Cell. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1172\/JCI71606","article-title":"Mechanisms of lymphatic metastasis","volume":"124","author":"Karaman","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1126\/science.aal3662","article-title":"Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice","volume":"359","author":"Brown","year":"2018","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1126\/science.aal3622","article-title":"Lymph node metastases can invade local blood vessels, exit the node, and colonize distant organs in mice","volume":"359","author":"Pereira","year":"2018","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.3892\/ijo.2016.3709","article-title":"Antiangiogenic cancer treatment: The great discovery and greater complexity (Review)","volume":"49","author":"Maj","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1159\/000488087","article-title":"Anti-Angiogenics: Current Situation and Future Perspectives","volume":"41","author":"Zirlik","year":"2018","journal-title":"Oncol. Res. Treat."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.jacc.2020.05.076","article-title":"Role of Cardiac Lymphatics in Myocardial Edema and Fibrosis","volume":"76","author":"Brakenhielm","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.ijrobp.2019.07.054","article-title":"Radiation Dose-Dependent Changes in Lymphatic Remodeling","volume":"105","author":"Kwon","year":"2019","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.jpedsurg.2019.02.026","article-title":"Lymphatic network remodeling after small bowel resection","volume":"54","author":"Onufer","year":"2019","journal-title":"J. Pediatr. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1161\/ATVBAHA.120.314370","article-title":"Lymphatic and Immune Cell Cross-Talk Regulates Cardiac Recovery After Experimental Myocardial Infarction","volume":"40","author":"Houssari","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1172\/JCI71607","article-title":"Inflammation-associated lymphangiogenesis: A double-edged sword?","volume":"124","author":"Kim","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s00005-015-0349-7","article-title":"Lymphangiogenesis and Inflammation\u2014Looking for the \u201cMissing Pieces\u201d of the Puzzle","volume":"63","author":"Cimpean","year":"2015","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1016\/S0002-9440(10)65021-3","article-title":"Vascular Endothelial Growth Factor Receptor-3 in Lymphangiogenesis in Wound Healing","volume":"156","author":"Paavonen","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.biomaterials.2017.03.033","article-title":"Local induction of lymphangiogenesis with engineered fibrin-binding VEGF-C promotes wound healing by increasing immune cell trafficking and matrix remodeling","volume":"131","author":"Briquez","year":"2017","journal-title":"Biomaterials"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1007\/s00417-001-0384-4","article-title":"Contribution of lymphatic drainage system in corneal allograft rejection in mice","volume":"239","author":"Hoffmann","year":"2001","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.survophthal.2017.12.008","article-title":"Angiogenesis and lymphangiogenesis in corneal transplantation\u2014A review","volume":"63","author":"Zhong","year":"2018","journal-title":"Surv. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kinashi, H., Ito, Y., Sun, T., Katsuno, T., and Takei, Y. (2018). Roles of the TGF-\u03b2\u2013VEGF-C Pathway in Fibrosis-Related Lymphangiogenesis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092487"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1097\/SLA.0b013e31826ed043","article-title":"Lymph Node Transfer and Perinodal Lymphatic Growth Factor Treatment for Lymphedema","volume":"257","author":"Honkonen","year":"2013","journal-title":"Ann. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.jss.2015.02.031","article-title":"Growth factor therapy and lymph node graft for lymphedema","volume":"196","author":"Tervala","year":"2015","journal-title":"J. Surg. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1177\/1947601911423028","article-title":"Lymphangiogenesis and Cancer","volume":"2","author":"Christiansen","year":"2011","journal-title":"Genes Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1146\/annurev-med-051419-114417","article-title":"Lymphatic Vasculature: An Emerging Therapeutic Target and Drug Delivery Route","volume":"72","author":"Xu","year":"2021","journal-title":"Annu. Rev. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.cell.2010.01.045","article-title":"Lymphangiogenesis: Molecular Mechanisms and Future Promise","volume":"140","author":"Tammela","year":"2010","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nrc863","article-title":"Lymphangiogenesis and cancer metastasis","volume":"2","author":"Stacker","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e1265718","DOI":"10.1080\/2162402X.2016.1265718","article-title":"A specific immune and lymphatic profile characterizes the pre-metastatic state of the sentinel lymph node in patients with early cervical cancer","volume":"6","author":"Balsat","year":"2017","journal-title":"OncoImmunology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1126\/science.aai8515","article-title":"Origins of lymphatic and distant metastases in human colorectal cancer","volume":"357","author":"Naxerova","year":"2017","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.coi.2018.03.018","article-title":"Multiple roles of lymphatic vessels in tumor progression","volume":"53","author":"Ma","year":"2018","journal-title":"Curr. Opin. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5987","DOI":"10.1007\/s00018-021-03873-z","article-title":"The pre-metastatic niche in lymph nodes: Formation and characteristics","volume":"78","author":"Gillot","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/S0140-6736(97)08260-3","article-title":"Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: A randomised trial","volume":"351","author":"Cascinelli","year":"1998","journal-title":"Lancet"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3396","DOI":"10.1245\/s10434-009-0659-2","article-title":"The Role of Lymph Node Metastasis in the Systemic Dissemination of Breast Cancer","volume":"16","author":"Nathanson","year":"2009","journal-title":"Ann. Surg. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.addr.2015.12.011","article-title":"Tumor lymphangiogenesis and new drug development","volume":"99","author":"Dieterich","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s00280-016-3134-3","article-title":"Phase 1 study of the anti-vascular endothelial growth factor receptor 3 monoclonal antibody LY3022856\/IMC-3C5 in patients with advanced and refractory solid tumors and advanced colorectal cancer","volume":"78","author":"Saif","year":"2016","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1517\/13543784.2016.1161754","article-title":"Novel anti-angiogenic therapeutic strategies in colorectal cancer","volume":"25","author":"Tampellini","year":"2016","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"379","DOI":"10.21037\/gs.2017.11.04","article-title":"Breast cancer-related lymphedema: Risk factors, precautionary measures, and treatments","volume":"7","author":"Gillespie","year":"2018","journal-title":"Gland Surg."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Torgbenu, E., Luckett, T., Buhagiar, M.A., Chang, S., and Phillips, J. (2020). Prevalence and incidence of cancer related lymphedema in low and middle-income countries: A systematic review and meta-analysis. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-07079-7"},{"key":"ref_40","unstructured":"Manrique, O.J., Bustos, S.S., Ciudad, P., Adabi, K., Chen, W.F., Forte, A.J., Cheville, A.L., Jakub, J.W., McLaughlin, S.A., and Chen, H.-C. (2020). Overview of Lymphedema for Physicians and Other Clinicians: A Review of Fundamental Concepts. Mayo Clin. Proc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"51","DOI":"10.5152\/turkjsurg.2017.3870","article-title":"Lymphedema: From diagnosis to treatment","volume":"33","author":"Kayiran","year":"2017","journal-title":"Turk. J. Surg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1447-073X.2006.00142.x","article-title":"Lymphangiogenesis and expression of specific molecules as lymphatic endothelial cell markers","volume":"81","author":"Kato","year":"2006","journal-title":"Anat. Sci. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1196\/annals.1413.001","article-title":"Markers for Microscopic Imaging of Lymphangiogenesis and Angiogenesis","volume":"1131","author":"Baluk","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/S0002-9440(10)63851-5","article-title":"Identification of Vascular Lineage-Specific Genes by Transcriptional Profiling of Isolated Blood Vascular and Lymphatic Endothelial Cells","volume":"162","author":"Hirakawa","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1096\/fj.09-132852","article-title":"Lymphangiogenesis: In vitro and in vivo models","volume":"24","year":"2010","journal-title":"FASEB J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/nrc4029","article-title":"The mathematics of cancer: Integrating quantitative models","volume":"15","author":"Altrock","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jtbi.2013.04.037","article-title":"A review of mathematical models for the formation of vascular networks","volume":"333","author":"Scianna","year":"2013","journal-title":"J. Theor. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Jean-Quartier, C., Jeanquartier, F., Jurisica, I., and Holzinger, A. (2018). In silico cancer research towards 3R. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4302-0"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"37","DOI":"10.18203\/2349-3259.ijct20161408","article-title":"In silico clinical trials: How computer simulation will transform the biomedical industry","volume":"3","author":"Viceconti","year":"2016","journal-title":"Int. J. Clin. Trials"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/nrc3677","article-title":"Lymphangiogenesis and lymphatic vessel remodelling in cancer","volume":"14","author":"Stacker","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1146\/annurev.pathmechdis.3.121806.151515","article-title":"Molecular Biology and Pathology of Lymphangiogenesis","volume":"3","author":"Karpanen","year":"2008","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1111\/j.1582-4934.2009.00834.x","article-title":"Lymphangiogenesis and cancer metastasis","volume":"13","author":"Mumprecht","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/dvdy.24227","article-title":"VEGFR signaling during lymphatic vascular development: From progenitor cells to functional vessels","volume":"244","author":"Secker","year":"2015","journal-title":"Dev. Dyn."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1172\/JCI71603","article-title":"Lymphangiogenic factors, mechanisms, and applications","volume":"124","author":"Zheng","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"105562","DOI":"10.1016\/j.biocel.2019.105562","article-title":"Lymphatic and blood systems: Identical or fraternal twins?","volume":"114","author":"Morfoisse","year":"2019","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5178","DOI":"10.1038\/s41467-018-07514-1","article-title":"uPARAP\/Endo180 receptor is a gatekeeper of VEGFR-2\/VEGFR-3 heterodimerisation during pathological lymphangiogenesis","volume":"9","author":"Morfoisse","year":"2018","journal-title":"Nat. Commun"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/modpathol.3880033","article-title":"Vascular Endothelial Growth Factor Receptor-3 (VEGFR-3): A Marker of Vascular Tumors with Presumed Lymphatic Differentiation, Including Kaposi\u2019s Sarcoma, Kaposiform and Dabska-Type Hemangioendotheliomas, and a Subset of Angiosarcomas","volume":"13","author":"Folpe","year":"2000","journal-title":"Mod. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.matbio.2018.02.001","article-title":"Hyaluronan in the lymphatics: The key role of the hyaluronan receptor LYVE-1 in leucocyte trafficking","volume":"78\u201379","author":"Jackson","year":"2019","journal-title":"Matrix Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0002-9440(10)65285-6","article-title":"Angiosarcomas Express Mixed Endothelial Phenotypes of Blood and Lymphatic Capillaries: Podoplanin as a Specific Marker for Lymphatic Endothelium","volume":"154","author":"Soleiman","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/dvdy.10163","article-title":"Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate","volume":"225","author":"Hong","year":"2002","journal-title":"Dev. Dyn."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1056\/NEJMoa020128","article-title":"Twenty-Five-Year Follow-up of a Randomized Trial Comparing Radical Mastectomy, Total Mastectomy, and Total Mastectomy Followed by Irradiation","volume":"347","author":"Fisher","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1245\/s10434-006-9234-2","article-title":"Regional Lymph Node Metastases; a Singular Manifestation of the Process of Clinical Metastases in Cancer: Contemporary Animal Research and Clinical Reports Suggest Unifying Concepts","volume":"14","author":"Cady","year":"2007","journal-title":"Ann. Surg. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.ccell.2014.10.006","article-title":"Antiangiogenesis Strategies Revisited: From Starving Tumors to Alleviating Hypoxia","volume":"26","author":"Jain","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1007\/BF02620930","article-title":"Tissue culture of human and canine thoracic duct endothelium","volume":"21","author":"Gnepp","year":"1985","journal-title":"In Vitro Cell. Dev. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1089\/lrb.2006.4.119","article-title":"Molecular Profile and Proliferative Responses of Rat Lymphatic Endothelial Cells in Culture","volume":"4","author":"Whitehurst","year":"2006","journal-title":"Lymphat. Res. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1365-2613.2008.00633.x","article-title":"A critical analysis of current in vitro and in vivo angiogenesis assays","volume":"90","author":"Staton","year":"2009","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13045-017-0484-1","article-title":"Targeting VEGFR-3\/-2 signaling pathways with AD0157: A potential strategy against tumor-associated lymphangiogenesis and lymphatic metastases","volume":"10","author":"Paupert","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"170009","DOI":"10.1038\/sdata.2017.9","article-title":"Systematic high-content genome-wide RNAi screens of endothelial cell migration and morphology","volume":"4","author":"Williams","year":"2017","journal-title":"Sci. Data"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.biomaterials.2015.11.027","article-title":"Cell-based approach for 3D reconstruction of lymphatic capillaries in vitro reveals distinct functions of HGF and VEGF-C in lymphangiogenesis","volume":"78","author":"Gibot","year":"2016","journal-title":"Biomaterials"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nmeth.1205","article-title":"Modeling lymphangiogenesis in a three-dimensional culture system","volume":"5","author":"Blacher","year":"2008","journal-title":"Nat. Methods"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Henderson, A.R., Choi, H., and Lee, E. (2020). Blood and Lymphatic Vasculatures On-Chip Platforms and Their Applications for Organ-Specific In Vitro Modeling. Micromachines, 11.","DOI":"10.3390\/mi11020147"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1016\/j.yexcr.2013.01.016","article-title":"Regulation of lymphatic vascular morphogenesis: Implications for pathological (tumor) lymphangiogenesis","volume":"319","author":"Makinen","year":"2013","journal-title":"Exp. Cell Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.mvr.2004.08.002","article-title":"Interstitial flow differentially stimulates blood and lymphatic endothelial cell morphogenesis in vitro","volume":"68","author":"Ng","year":"2004","journal-title":"Microvasc. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1161\/01.RES.0000065621.69843.49","article-title":"Interstitial Flow as a Guide for Lymphangiogenesis","volume":"92","author":"Boardman","year":"2003","journal-title":"Circ. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/bit.21185","article-title":"Engineered blood and lymphatic capillaries in 3-D VEGF-fibrin-collagen matrices with interstitial flow","volume":"96","author":"Helm","year":"2007","journal-title":"Biotechnol. Bioeng."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1039\/C5IB00085H","article-title":"An in vitro model of the tumor\u2013lymphatic microenvironment with simultaneous transendothelial and luminal flows reveals mechanisms of flow enhanced invasion","volume":"7","author":"Pisano","year":"2015","journal-title":"Integr. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"221ra14","DOI":"10.1126\/scitranslmed.3006894","article-title":"Bioengineering Dermo-Epidermal Skin Grafts with Blood and Lymphatic Capillaries","volume":"6","author":"Marino","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1021\/acsbiomaterials.0c01378","article-title":"Long-Lived Human Lymphatic Endothelial Cells to Study Lymphatic Biology and Lymphatic Vessel\/Tumor Coculture in a 3D Microfluidic Model","volume":"7","author":"Frenkel","year":"2021","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.biomaterials.2015.11.019","article-title":"Three-dimensional biomimetic model to reconstitute sprouting lymphangiogenesis in vitro","volume":"78","author":"Kim","year":"2016","journal-title":"Biomaterials"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ymeth.2020.04.003","article-title":"Investigating lymphangiogenesis in a sacrificially bioprinted volumetric model of breast tumor tissue","volume":"190","author":"Liu","year":"2021","journal-title":"Methods"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1038\/nprot.2017.025","article-title":"Tissue-engineered 3D human lymphatic microvascular network for in vitro studies of lymphangiogenesis","volume":"12","author":"Gibot","year":"2017","journal-title":"Nat. Protoc."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1007\/s40883-018-0054-2","article-title":"Cooperative Effects of Vascular Angiogenesis and Lymphangiogenesis","volume":"4","author":"Osaki","year":"2018","journal-title":"Regen. Eng. Transl. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2007199","DOI":"10.1002\/adfm.202007199","article-title":"Engineering New Microvascular Networks On-Chip: Ingredients, Assembly, and Best Practices","volume":"31","author":"Tronolone","year":"2021","journal-title":"Adv. Funct. Mater."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e2101931118","DOI":"10.1073\/pnas.2101931118","article-title":"Investigating lymphangiogenesis in vitro and in vivo using engineered human lymphatic vessel networks","volume":"118","author":"Landau","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.2147\/CMAR.S302565","article-title":"Application of Animal Models in Cancer Research: Recent Progress and Future Prospects","volume":"13","author":"Li","year":"2021","journal-title":"Cancer Manag. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"7828","DOI":"10.1158\/0008-5472.CAN-08-1488","article-title":"Suppression of Prostate Cancer Nodal and Systemic Metastasis by Blockade of the Lymphangiogenic Axis","volume":"68","author":"Burton","year":"2008","journal-title":"Cancer Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1093\/jnci\/djs009","article-title":"Effects of Angiopoietin-2-Blocking Antibody on Endothelial Cell\u2013Cell Junctions and Lung Metastasis","volume":"104","author":"Holopainen","year":"2012","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5459","DOI":"10.1158\/1078-0432.CCR-07-5270","article-title":"Multi-Kinase Inhibitor E7080 Suppresses Lymph Node and Lung Metastases of Human Mammary Breast Tumor MDA-MB-231 via Inhibition of Vascular Endothelial Growth Factor-Receptor (VEGF-R) 2 and VEGF-R3 Kinase","volume":"14","author":"Matsui","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4499","DOI":"10.1038\/onc.2011.602","article-title":"Interaction of tumor cells and lymphatic vessels in cancer progression","volume":"31","author":"Alitalo","year":"2012","journal-title":"Oncogene"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"E2665","DOI":"10.1073\/pnas.1206036109","article-title":"Phenotype-based high-content chemical library screening identifies statins as inhibitors of in vivo lymphangiogenesis","volume":"109","author":"Schulz","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s00595-004-2896-0","article-title":"Vascular Endothelial Growth Factor C Promotes Lymph Node Metastasis in a Rectal Cancer Orthotopic Model","volume":"35","author":"Kawakami","year":"2005","journal-title":"Surg. Today"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1196\/annals.1413.005","article-title":"Animal Models for the Molecular and Mechanistic Study of Lymphatic Biology and Disease","volume":"1131","author":"Shin","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1002\/ijc.10283","article-title":"VEGF-C induced lymphangiogenesis is associated with lymph node metastasis in orthotopic MCF-7 tumors","volume":"98","author":"Mattila","year":"2002","journal-title":"Int. J. Cancer"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/84643","article-title":"Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis","volume":"7","author":"Skobe","year":"2001","journal-title":"Nat. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1093\/emboj\/20.4.672","article-title":"Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis","volume":"20","author":"Mandriota","year":"2001","journal-title":"EMBO J."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/84635","article-title":"VEGF-D promotes the metastatic spread of tumor cells via the lymphatics","volume":"7","author":"Stacker","year":"2001","journal-title":"Nat. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ccr.2011.12.026","article-title":"VEGF-D Promotes Tumor Metastasis by Regulating Prostaglandins Produced by the Collecting Lymphatic Endothelium","volume":"21","author":"Karnezis","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4739","DOI":"10.1158\/0008-5472.CAN-04-4576","article-title":"Vascular Endothelial Cell Growth Factor Receptor 3\u2013Mediated Activation of Lymphatic Endothelium Is Crucial for Tumor Cell Entry and Spread via Lymphatic Vessels","volume":"65","author":"He","year":"2005","journal-title":"Cancer Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/1476-4598-10-36","article-title":"Soluble vascular endothelial growth factor receptor-3 suppresses lymphangiogenesis and lymphatic metastasis in bladder cancer","volume":"10","author":"Yang","year":"2011","journal-title":"Mol. Cancer"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1111\/cas.14531","article-title":"Soluble Vegfr3 gene therapy suppresses multi-organ metastasis in a mouse mammary cancer model","volume":"111","author":"Shibata","year":"2020","journal-title":"Cancer Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4565","DOI":"10.1182\/blood-2011-09-380006","article-title":"Blocking ephrinB2 with highly specific antibodies inhibits angiogenesis, lymphangiogenesis, and tumor growth","volume":"119","author":"Ferreiro","year":"2012","journal-title":"Blood"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1083\/jcb.200903137","article-title":"Neuropilin-2 mediates VEGF-C-induced lymphatic sprouting together with VEGFR3","volume":"188","author":"Xu","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ccr.2008.01.029","article-title":"Blocking Neuropilin-2 Function Inhibits Tumor Cell Metastasis","volume":"13","author":"Caunt","year":"2008","journal-title":"Cancer Cell"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1158\/1535-7163.MCT-14-0469-T","article-title":"An In Vivo Antilymphatic Screen in Zebrafish Identifies Novel Inhibitors of Mammalian Lymphangiogenesis and Lymphatic-Mediated Metastasis","volume":"13","author":"Astin","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"241","DOI":"10.7150\/jca.35448","article-title":"Inhibition of Tumor Lymphangiogenesis is an Important Part that EGFR-TKIs Play in the Treatment of NSCLC","volume":"11","author":"Zhang","year":"2020","journal-title":"J. Cancer"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.molonc.2013.02.007","article-title":"Mouse models for studying angiogenesis and lymphangiogenesis in cancer","volume":"7","author":"Eklund","year":"2013","journal-title":"Mol. Oncol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/978-1-4939-7595-2_20","article-title":"Ear Sponge Assay: A Method to Investigate Angiogenesis and Lymphangiogenesis in Mice","volume":"Volume 1731","author":"Kridelka","year":"2018","journal-title":"Proteases and Cancer: Methods and Protocols"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"41494","DOI":"10.1038\/srep41494","article-title":"Modeling pre-metastatic lymphvascular niche in the mouse ear sponge assay","volume":"7","author":"Blacher","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1203\/PDR.0b013e318186e609","article-title":"Zebrafish as a Developmental Model Organism for Pedriatric Research","volume":"64","author":"Veldman","year":"2008","journal-title":"Pediatr. Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"294","DOI":"10.3389\/fnmol.2018.00294","article-title":"Zebrafish Models of Neurodevelopmental Disorders: Past, Present, and Future","volume":"11","author":"Sakai","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"19085","DOI":"10.1038\/s41598-020-75917-6","article-title":"A zebrafish functional genomics model to investigate the role of human A20 variants in vivo","volume":"10","author":"Cultrone","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_112","first-page":"94","article-title":"Benefits of Zebrafish Xenograft Models in Cancer Research","volume":"9","author":"Chen","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Gamble, J., Elson, D., Greenwood, J., Tanguay, R., and Kolluri, S. (2021). The Zebrafish Xenograft Models for Investigating Cancer and Cancer Therapeutics. Biology, 10.","DOI":"10.3390\/biology10040252"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/978-1-60761-898-0_14","article-title":"Zebrafish (Danio rerio) as a Model Organism for Dementia","volume":"Volume 48","author":"Willemsen","year":"2011","journal-title":"Animal Models of Dementia"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Hason, M., and Bart\u016fn\u011bk, P. (2019). Zebrafish Models of Cancer\u2014New Insights on Modeling Human Cancer in a Non-Mammalian Vertebrate. Genes, 10.","DOI":"10.3390\/genes10110935"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1016\/j.cell.2019.04.004","article-title":"Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish","volume":"177","author":"Yan","year":"2019","journal-title":"Cell"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.stem.2007.11.002","article-title":"Transparent Adult Zebrafish as a Tool for In Vivo Transplantation Analysis","volume":"2","author":"White","year":"2008","journal-title":"Cell Stem Cell"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.devcel.2017.08.015","article-title":"How to Plumb a Pisces: Understanding Vascular Development and Disease Using Zebrafish Embryos","volume":"42","author":"Hogan","year":"2017","journal-title":"Dev. Cell"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"10358","DOI":"10.1038\/ncomms10358","article-title":"Imaging tumour cell heterogeneity following cell transplantation into optically clear immune-deficient zebrafish","volume":"7","author":"Tang","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.devcel.2019.01.014","article-title":"Studying the Fate of Tumor Extracellular Vesicles at High Spatiotemporal Resolution Using the Zebrafish Embryo","volume":"48","author":"Hyenne","year":"2019","journal-title":"Dev. Cell"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"145","DOI":"10.12997\/jla.2021.10.2.145","article-title":"Zebrafish Vascular Development: General and Tissue-Specific Regulation","volume":"10","author":"Nakajima","year":"2021","journal-title":"J. Lipid Atheroscler."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1111\/micc.12289","article-title":"Utilizing Zebrafish to Identify Anti-(Lymph)Angiogenic Compounds for Cancer Treatment: Promise and Future Challenges","volume":"23","author":"Okuda","year":"2016","journal-title":"Microcirculation"},{"key":"ref_123","first-page":"56","article-title":"Zebrafish as an Emerging Model Organism to Study Angiogenesis in Development and Regeneration","volume":"7","author":"Aedo","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_124","first-page":"239","article-title":"Imaging Cancer Angiogenesis and Metastasis in a Zebrafish Embryo Model","volume":"Volume 916","author":"Tulotta","year":"2016","journal-title":"Cancer and Zebrafish: Mechanisms, Techniques, and Models"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Astin, J.W., and Crosier, P.S. (2016). Lymphatics, Cancer and Zebrafish. Cancer and Zebrafish: Mechanisms, Techniques, and Models, Springer.","DOI":"10.1007\/978-3-319-30654-4_9"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1016\/j.cub.2006.05.026","article-title":"Development of the Zebrafish Lymphatic System Requires Vegfc Signaling","volume":"16","author":"Gjini","year":"2006","journal-title":"Curr. Biol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3785","DOI":"10.1242\/dev.137901","article-title":"Vegfc acts through ERK to induce sprouting and differentiation of trunk lymphatic progenitors","volume":"143","author":"Shin","year":"2016","journal-title":"Development"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1242\/dev.146969","article-title":"Vegfd modulates both angiogenesis and lymphangiogenesis during zebrafish embryonic development","volume":"144","author":"Bower","year":"2017","journal-title":"Development"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41536-019-0079-2","article-title":"Vegfc\/d-dependent regulation of the lymphatic vasculature during cardiac regeneration is influenced by injury context","volume":"4","author":"Vivien","year":"2019","journal-title":"npj Regen. Med."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"e42881","DOI":"10.7554\/eLife.42881","article-title":"Yap1 promotes sprouting and proliferation of lymphatic progenitors downstream of Vegfc in the zebrafish trunk","volume":"8","author":"Grimm","year":"2019","journal-title":"eLife"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Okuda, K., Ng, M., Ruslan, N., Bower, N., Song, D., Chen, H., Baek, S., Crosier, P., Koltowska, K., and Astin, J. (2021). 3,4-Difluorobenzocurcumin Inhibits Vegfc-Vegfr3-Erk Signalling to Block Developmental Lymphangiogenesis in Zebrafish. Pharmaceuticals, 14.","DOI":"10.3390\/ph14070614"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"19459","DOI":"10.1038\/srep19459","article-title":"Intravital Imaging Reveals Dynamics of Lymphangiogenesis and Valvulogenesis","volume":"6","author":"Kang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Hong, M., Jung, E., Yang, S., Jung, W., Seong, Y.J., Park, E., Bramos, A., Kim, K.E., Lee, S., and Daghlian, G. (2016). Efficient Assessment of Developmental, Surgical and Pathological Lymphangiogenesis Using a Lymphatic Reporter Mouse and Its Embryonic Stem Cells. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157126"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1042\/BST20110722","article-title":"Intravital two-photon microscopy of lymphatic vessel development and function using a transgenic Prox1 promoter-directed mOrange2 reporter mouse","volume":"39","author":"Pollmann","year":"2011","journal-title":"Biochem. Soc. Trans."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1182\/blood-2010-07-298562","article-title":"Visualization of lymphatic vessels by Prox1-promoter directed GFP reporter in a bacterial artificial chromosome-based transgenic mouse","volume":"117","author":"Choi","year":"2011","journal-title":"Blood"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"5577","DOI":"10.1038\/s41598-017-06031-3","article-title":"Development and Characterization of A Novel Prox1-EGFP Lymphatic and Schlemm\u2019s Canal Reporter Rat","volume":"7","author":"Jung","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nature22977","article-title":"Whole-body imaging of lymphovascular niches identifies pre-metastatic roles of midkine","volume":"546","author":"Olmeda","year":"2017","journal-title":"Nature"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1101\/gad.615311","article-title":"Vascular endothelial growth factor receptor 3 directly regulates murine neurogenesis","volume":"25","author":"Calvo","year":"2011","journal-title":"Genes Dev."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/labinvest.2015.147","article-title":"Lymphatic endothelial lineage assemblage during corneal lymphangiogenesis","volume":"96","author":"Connor","year":"2016","journal-title":"Lab. Investig."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s10456-018-9629-2","article-title":"Fluorescent Reporter Transgenic Mice for In Vivo Live Imaging of Angiogenesis and Lymphangiogenesis","volume":"176","author":"Doh","year":"2018","journal-title":"Angiogenesis"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1161\/CIRCRESAHA.120.317372","article-title":"Live Imaging of Intracranial Lymphatics in the Zebrafish","volume":"128","author":"Castranova","year":"2021","journal-title":"Circ. Res."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Hoffman, S.J., Psaltis, P.J., Clark, K.J., Spoon, D.B., Chue, C.D., Ekker, S.C., and Simari, R.D. (2012). An In Vivo Method to Quantify Lymphangiogenesis in Zebrafish. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045240"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/nm1427","article-title":"Live imaging of lymphatic development in the zebrafish","volume":"12","author":"Yaniv","year":"2006","journal-title":"Nat. Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1093\/jnci\/dji023","article-title":"Imaging Angiogenesis: Applications and Potential for Drug Development","volume":"97","author":"Miller","year":"2005","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s10456-010-9178-9","article-title":"Imaging of angiogenesis","volume":"13","author":"MulderArjan","year":"2010","journal-title":"Angiogenesis"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Asabella, A.N., Altini, C., Ferrari, C., Rubini, G., and Di Palo, A. (2017). Multimodality Imaging in Tumor Angiogenesis: Present Status and Perspectives. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18091864"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.mvr.2014.06.006","article-title":"Imaging the lymphatic system","volume":"96","author":"Munn","year":"2014","journal-title":"Microvasc. Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1055\/s-0043-123937","article-title":"Role of Indocyanine Green in Fluorescence Imaging with Near-Infrared Light to Identify Sentinel Lymph Nodes, Lymphatic Vessels and Pathways Prior to Surgery\u2014A Critical Evaluation of Options","volume":"78","author":"Hackethal","year":"2018","journal-title":"Geburtshilfe Frauenheilkd."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Suami, H., Heydon-White, A., Mackie, H., Czerniec, S., Koelmeyer, L., and Boyages, J. (2019). A new indocyanine green fluorescence lymphography protocol for identification of the lymphatic drainage pathway for patients with breast cancer-related lymphoedema. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-6192-1"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1111\/wrr.12063","article-title":"Detection of lymphangiogenesis by near-infrared fluorescence imaging and responses to VEGF-C during healing in a mouse full-dermis thickness wound model","volume":"21","author":"Hall","year":"2013","journal-title":"Wound Repair Regen."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1002\/art.27464","article-title":"Near infrared lymphatic imaging demonstrates the dynamics of lymph flow and lymphangiogenesis during the acute vs. chronic phases of arthritis in mice","volume":"62","author":"Zhou","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"8842","DOI":"10.1158\/0008-5472.CAN-10-0896","article-title":"In vivo Imaging of Inflammation- and Tumor-Induced Lymph Node Lymphangiogenesis by Immuno\u2013Positron Emission Tomography","volume":"70","author":"Mumprecht","year":"2010","journal-title":"Cancer Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1007\/s00109-015-1351-6","article-title":"The lymph node pre-metastatic niche","volume":"93","author":"Sleeman","year":"2015","journal-title":"J. Mol. Med."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1016\/j.crad.2013.06.022","article-title":"Feasibility of MR imaging in evaluating breast cancer lymphangiogenesis using Polyethylene glycol-GoldMag nanoparticles","volume":"68","author":"Yang","year":"2013","journal-title":"Clin. Radiol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.addr.2020.08.013","article-title":"Imaging technology of the lymphatic system","volume":"170","author":"Polomska","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Elshikh, M., Moawad, A.W., Salem, U., Klimkowski, S.P., Hassan, T., Korivi, B.R., Jensen, C.T., Javadi, S., and Elsayes, K.M. (2021). Oncologic Imaging of the Lymphatic System: Current Perspective with Multi-Modality Imaging and New Horizon. Cancers, 13.","DOI":"10.3390\/cancers13184554"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"021005","DOI":"10.1115\/1.4037671","article-title":"Applicability Analysis of Validation Evidence for Biomedical Computational Models","volume":"2","author":"Pathmanathan","year":"2017","journal-title":"J. Verif. Valid. Uncert. Quantif."},{"key":"ref_158","unstructured":"ASME (2018). Assessing Credibility of Computational Modeling through Verification and Validation: Application to Medical Devices, ASME."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"101198","DOI":"10.1016\/j.jocs.2020.101198","article-title":"Cancer modeling: From mechanistic to data-driven approaches, and from fundamental insights to clinical applications","volume":"46","author":"Bekisz","year":"2020","journal-title":"J. Comput. Sci."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3389\/fbioe.2018.00165","article-title":"Computational Modeling and Reverse Engineering to Reveal Dominant Regulatory Interactions Controlling Osteochondral Differentiation: Potential for Regenerative Medicine","volume":"6","author":"Lesage","year":"2018","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"354","DOI":"10.3389\/fgene.2015.00354","article-title":"The (Mathematical) Modeling Process in Biosciences","volume":"6","author":"Torres","year":"2015","journal-title":"Front. Genet."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/bib\/bbs061","article-title":"Mathematical modeling of biological systems","volume":"14","author":"Motta","year":"2013","journal-title":"Brief. Bioinform."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1002\/psp4.12479","article-title":"Consideration of a Credibility Assessment Framework in Model-Informed Drug Development: Potential Application to Physiologically-Based Pharmacokinetic Modeling and Simulation","volume":"9","author":"Kuemmel","year":"2020","journal-title":"CPT Pharmacomet. Syst. Pharmacol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1080\/10739680802220331","article-title":"Computational and Mathematical Modeling of Angiogenesis","volume":"15","author":"Peirce","year":"2008","journal-title":"Microcirculation"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1051\/mmnp\/201510106","article-title":"Computational Models of Sprouting Angiogenesis and Cell Migration: Towards Multiscale Mechanochemical Models of Angiogenesis","volume":"10","author":"Heck","year":"2015","journal-title":"Math. Model. Nat. Phenom."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1023\/A:1006446020377","article-title":"Mathematical Modelling of Angiogenesis","volume":"50","author":"Chaplain","year":"2000","journal-title":"J. Neuro-Oncol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s00285-003-0262-2","article-title":"Mathematical modeling of tumor-induced angiogenesis","volume":"49","author":"Mantzaris","year":"2004","journal-title":"J. Math. Biol."},{"key":"ref_168","unstructured":"Levine, H.A., and Nilsen-Hamilton, M. (2005). Angiogenesis\u2014A Biochemical\/Mathematical Perspective. Tutorials in Mathematical Biosciences III: Cell Cycle, Proliferation, and Cancer, Springer."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Levine, H., and Sleeman, B. (2003). Modelling Tumour-Induced Angiogenesis. Cancer Modelling and Simulation, CRC Press.","DOI":"10.1201\/9780203494899.ch6"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1109\/MEMB.2009.931791","article-title":"Multiscale models of angiogenesis","volume":"28","author":"Qutub","year":"2009","journal-title":"IEEE Eng. Med. Biol. Mag."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/cas.13395","article-title":"Study on the tumor-induced angiogenesis using mathematical models","volume":"109","author":"Suzuki","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1088\/0951-7715\/23\/1\/R01","article-title":"Nonlinear modelling of cancer: Bridging the gap between cells and tumours","volume":"23","author":"Lowengrub","year":"2010","journal-title":"Nonlinearity"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/1350-4533(95)91885-K","article-title":"A mathematical model of flow through the terminal lymphatics","volume":"17","author":"Reddy","year":"1995","journal-title":"Med Eng. Phys."},{"key":"ref_174","first-page":"45","article-title":"Lymph circulation: Physiology, pharmacology, and biomechanics","volume":"14","author":"Reddy","year":"1986","journal-title":"Crit. Rev. Biomed. Eng."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0010-4825(77)90023-3","article-title":"A computer model of the lymphatic system","volume":"7","author":"Reddy","year":"1977","journal-title":"Comput. Biol. Med."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1159\/000158062","article-title":"Biomechanics of a Lymphatic Vessel","volume":"12","author":"Reddy","year":"1975","journal-title":"J. Vasc. Res."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/0026-2862(76)90013-3","article-title":"Mathematical model of the initial lymphatics","volume":"12","author":"Elhay","year":"1976","journal-title":"Microvasc. Res."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"H305","DOI":"10.1152\/ajpheart.00004.2008","article-title":"Modeling flow in collecting lymphatic vessels: One-dimensional flow through a series of contractile elements","volume":"295","author":"Macdonald","year":"2008","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Roose, T., and Tabor, G. (2012). Multiscale Modelling of Lymphatic Drainage. Multiscale Computer Modeling in Biomechanics and Biomedical Engineering, Springer.","DOI":"10.1007\/8415_2012_148"},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Mozokhina, A., and Savinkov, R. (2020). Mathematical Modelling of the Structure and Function of the Lymphatic System. Mathematics, 8.","DOI":"10.3390\/math8091467"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1051\/mmnp\/2018044","article-title":"Modelling lymph flow in the lymphatic system: From 0D to 1D spatial resolution","volume":"13","author":"Tretyakova","year":"2018","journal-title":"Math. Model. Nat. Phenom."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s11538-015-0128-y","article-title":"An Image-Based Model of Fluid Flow Through Lymph Nodes","volume":"78","author":"Cooper","year":"2016","journal-title":"Bull. Math. Biol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s10237-019-01238-x","article-title":"A computational model of a network of initial lymphatics and pre-collectors with permeable interstitium","volume":"19","author":"Ikhimwin","year":"2020","journal-title":"Biomech. Model. Mechanobiol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1142\/S0218202505003915","article-title":"Analysis of a mathematical model of tumor lymphangiogenesis","volume":"15","author":"Friedman","year":"2005","journal-title":"Math. Model. Methods Appl. Sci."},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Pepper, M.S., and Lolas, G. (2008). The Lymphatic Vascular System in Lymphangiogenesis Invasion and Metastasis A Mathematical Approach. Selected Topics in Cancer Modeling, Birkh\u00e4user.","DOI":"10.1007\/978-0-8176-4713-1_10"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/978-3-319-42023-3_6","article-title":"Modeling Proteolytically Driven Tumor Lymphangiogenesis","volume":"Volume 936","author":"Lolas","year":"2016","journal-title":"Systems Biology of Tumor Microenvironment: Quantitative Modeling and Simulations"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.3389\/fimmu.2018.02428","article-title":"Integrative Computational Modeling of the Lymph Node Stromal Cell Landscape","volume":"9","author":"Novkovic","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.4049\/jimmunol.1700377","article-title":"A Novel Computational Model Predicts Key Regulators of Chemokine Gradient Formation in Lymph Nodes and Site-Specific Roles for CCL19 and ACKR4","volume":"199","author":"Jafarnejad","year":"2017","journal-title":"J. Immunol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"104","DOI":"10.3389\/fbioe.2019.00104","article-title":"Mathematical Modeling Reveals That the Administration of EGF Can Promote the Elimination of Lymph Node Metastases by PD-1\/PD-L1 Blockade","volume":"7","author":"Benchaib","year":"2019","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jtbi.2012.11.031","article-title":"The effect of interstitial pressure on tumor growth: Coupling with the blood and lymphatic vascular systems","volume":"320","author":"Wu","year":"2013","journal-title":"J. Theor. Biol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1089\/lrb.2015.0028","article-title":"Modeling Lymph Flow and Fluid Exchange with Blood Vessels in Lymph Nodes","volume":"13","author":"Jafarnejad","year":"2015","journal-title":"Lymphat. Res. Biol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"111004","DOI":"10.1115\/1.3212108","article-title":"A Two-Dimensional Computational Model of Lymph Transport Across Primary Lymphatic Valves","volume":"131","author":"Galie","year":"2009","journal-title":"J. Biomech. Eng."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1098\/rsif.2011.0751","article-title":"Modelling the lymphatic system: Challenges and opportunities","volume":"9","author":"Margaris","year":"2012","journal-title":"J. R. Soc. Interface"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1007\/s13239-011-0054-6","article-title":"Engineering the Lymphatic System","volume":"2","author":"Nipper","year":"2011","journal-title":"Cardiovasc. Eng. Technol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"7347","DOI":"10.1113\/JP274842","article-title":"Calcium and electrical dynamics in lymphatic endothelium","volume":"595","author":"Behringer","year":"2017","journal-title":"J. Physiol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1007\/s10237-018-1050-7","article-title":"A one-dimensional mathematical model of collecting lymphatics coupled with an electro-fluid-mechanical contraction model and valve dynamics","volume":"17","author":"Contarino","year":"2018","journal-title":"Biomech. Model. Mechanobiol."},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Sibler, E., He, Y., Ducoli, L., Keller, N., Fujimoto, N., Dieterich, L., and Detmar, M. (2021). Single-Cell Transcriptional Heterogeneity of Lymphatic Endothelial Cells in Normal and Inflamed Murine Lymph Nodes. Cells, 10.","DOI":"10.3390\/cells10061371"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"52","DOI":"10.3389\/fcvm.2020.00052","article-title":"A Single-Cell Transcriptional Roadmap of the Mouse and Human Lymph Node Lymphatic Vasculature","volume":"7","author":"Xiang","year":"2020","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Fujimoto, N., He, Y., D\u2019Addio, M., Tacconi, C., Detmar, M., and Dieterich, L.C. (2020). Single-cell mapping reveals new markers and functions of lymphatic endothelial cells in lymph nodes. PLOS Biol., 18.","DOI":"10.1101\/2020.01.09.900241"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"816","DOI":"10.3389\/fimmu.2019.00816","article-title":"Comparative Transcriptomic Analysis Identifies a Range of Immunologically Related Functional Elaborations of Lymph Node Associated Lymphatic and Blood Endothelial Cells","volume":"10","author":"Berendam","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.immuni.2019.06.027","article-title":"Single-Cell Survey of Human Lymphatics Unveils Marked Endothelial Cell Heterogeneity and Mechanisms of Homing for Neutrophils","volume":"51","author":"Takeda","year":"2019","journal-title":"Immunity"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"21244","DOI":"10.1038\/s41598-020-76394-7","article-title":"Metabolomics revealed the influence of breast cancer on lymphatic endothelial cell metabolism, metabolic crosstalk, and lymphangiogenic signaling in co-culture","volume":"10","author":"Millar","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_203","doi-asserted-by":"crossref","unstructured":"Popova, T.G., Espina, V., Zhou, W., Mueller, C., Liotta, L., and Popov, S.G. (2014). Whole Proteome Analysis of Mouse Lymph Nodes in Cutaneous Anthrax. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110873"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"100318","DOI":"10.1016\/j.xcrm.2021.100318","article-title":"In-depth proteomics analysis of sentinel lymph nodes from individuals with endometrial cancer","volume":"2","author":"Aboulouard","year":"2021","journal-title":"Cell Rep. Med."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s11538-017-0248-7","article-title":"A Mathematical Model of Lymphangiogenesis in a Zebrafish Embryo","volume":"79","author":"Wertheim","year":"2017","journal-title":"Bull. Math. Biol."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1007\/s11538-016-0205-x","article-title":"Spatio-temporal Models of Lymphangiogenesis in Wound Healing","volume":"78","author":"Bianchi","year":"2016","journal-title":"Bull. Math. Biol."},{"key":"ref_207","doi-asserted-by":"crossref","unstructured":"Tretyakova, R., Savinkov, R., Lobov, G., and Bocharov, G. (2017). Developing Computational Geometry and Network Graph Models of Human Lymphatic System. Computation, 6.","DOI":"10.3390\/computation6010001"},{"key":"ref_208","unstructured":"(2021, September 02). Leukemia and Lymphoma Society. Available online: https:\/\/www.lls.org\/3d-model-library\/lymph-node-anatomy-3d-model."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41467-019-14134-w","article-title":"Cancer-associated fibroblast heterogeneity in axillary lymph nodes drives metastases in breast cancer through complementary mechanisms","volume":"11","author":"Pelon","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1002\/psp4.12669","article-title":"Scientific and regulatory evaluation of mechanistic in silico drug and disease models in drug development: Building model credibility","volume":"10","author":"Musuamba","year":"2021","journal-title":"CPT Pharmacomet. Syst. Pharmacol."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.1109\/JBHI.2021.3090469","article-title":"Possible Contexts of Use for In Silico Trials Methodologies: A Consensus-Based Review","volume":"25","author":"Viceconti","year":"2021","journal-title":"IEEE J. Biomed. Health Inform."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"2002030","DOI":"10.1002\/advs.202002030","article-title":"Is it Time for Reviewer 3 to Request Human Organ Chip Experiments Instead of Animal Validation Studies?","volume":"7","author":"Ingber","year":"2020","journal-title":"Adv. Sci."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1093\/bib\/bby043","article-title":"In silico clinical trials: Concepts and early adoptions","volume":"20","author":"Pappalardo","year":"2019","journal-title":"Brief. Bioinform."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/6\/1525\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:37:34Z","timestamp":1760135854000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/6\/1525"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,16]]},"references-count":213,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["cancers14061525"],"URL":"https:\/\/doi.org\/10.3390\/cancers14061525","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,16]]}}}